tbuckley/cabot-search huggingface dataset:
Measurement theory and paleobiology
Authors: Kjetil Lysne Voje, James G. Saulsbury, Jostein Starrfelt, Daniel Varajão Latorre, Alexis Rojas, Vilde Bruhn Kinneberg, Lee Hsiang Liow, Connor J. Wilson, Erin E. Saupe, Mark Grabowski
Journal: Trends in Ecology & Evolution (2023)

Measurement theory, a branch of applied mathematics, offers guiding principles for extracting meaning from empirical observations and is applicable to any science involving measurements. Measurement theory is highly relevant in paleobiology because statistical approaches assuming ratio-scaled variables are commonly used on data belonging to nominal and ordinal scale types. We provide an informal introduction to representational measurement theory and argue for its importance in robust scientific inquiry. Although measurement theory is widely applicable in paleobiology research, we use the study of disparity to illustrate measurement theoretical challenges in the quantitative study of the fossil record. Respecting the inherent properties of different measurements enables meaningful inferences about evolutionary and ecological processes from paleontological data.
A Review of Energy Supply for Biomachine Hybrid Robots
Authors: Zhiyun Ma, Jieliang Zhao, Li Yu, Mengdan Yan, Lulu Liang, Xiangbing Wu, Mengdi Xu, Wenzhong Wang, Shaoze Yan
Journal: Cyborg and Bionic Systems (2023)

Biomachine hybrid robots have been proposed for important scenarios, such as wilderness rescue, ecological monitoring, and hazardous area surveying. The energy supply unit used to power the control backpack carried by these robots determines their future development and practical application. Current energy supply devices for control backpacks are mainly chemical batteries. To achieve self-powered devices, researchers have developed solar energy, bioenergy, biothermal energy, and biovibration energy harvesters. This review provides an overview of research in the development of chemical batteries and self-powered devices for biomachine hybrid robots. Various batteries for different biocarriers and the entry points for the design of self-powered devices are outlined in detail. Finally, an overview of the future challenges and possible directions for the development of energy supply devices used to biomachine hybrid robots is provided.
Rational Design of Bioactive Materials for Bone Hemostasis and Defect Repair
Authors: Yuqi Gai, Yue Yin, Ling Guan, Shengchang Zhang, Jiatian Chen, Junyuan Yang, Huaijuan Zhou, Jinhua Li
Journal: Cyborg and Bionic Systems (2023)

Everyday unnatural events such as trauma, accidents, military conflict, disasters, and even medical malpractice create open wounds and massive blood loss, which can be life-threatening. Fractures and large bone defects are among the most common types of injuries. Traditional treatment methods usually involve rapid hemostasis and wound closure, which are convenient and fast but may result in various complications such as nerve injury, deep infection, vascular injury, and deep hematomas. To address these complications, various studies have been conducted on new materials that can be degraded in the body and reduce inflammation and abscesses in the surgical area. This review presents the latest research progress in biomaterials for bone hemostasis and repair. The mechanisms of bone hemostasis and bone healing are first introduced and then principles for rational design of biomaterials are summarized. After providing representative examples of hemostatic biomaterials for bone repair, future challenges and opportunities in the field are proposed.
FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia
Authors: Kasidy K. Dobish, Karli J. Wittorf, Samantha A. Swenson, Dalton C. Bean, Catherine M. Gavile, Nicholas T. Woods, Gargi Ghosal, R. Katherine Hyde, Shannon M. Buckley
Journal: Leukemia (2023)

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by clonal expansion of myeloid blasts in the bone marrow (BM). Despite advances in therapy, the prognosis for AML patients remains poor, and there is a need to identify novel molecular pathways regulating tumor cell survival and proliferation. F-box ubiquitin E3 ligase, FBXO21, has low expression in AML, but expression correlates with survival in AML patients and patients with higher expression have poorer outcomes. Silencing FBXO21 in human-derived AML cell lines and primary patient samples leads to differentiation, inhibition of tumor progression, and sensitization to chemotherapy agents. Additionally, knockdown of FBXO21 leads to up-regulation of cytokine signaling pathways. Through a mass spectrometry-based proteomic analysis of FBXO21 in AML, we identified that FBXO21 ubiquitylates p85α, a regulatory subunit of the phosphoinositide 3-kinase (PI3K) pathway, for degradation resulting in decreased PI3K signaling, dimerization of free p85α and ERK activation. These findings reveal the ubiquitin E3 ligase, FBXO21, plays a critical role in regulating AML pathogenesis, specifically through alterations in PI3K via regulation of p85α protein stability.
Re: Stavros Gravas, Mauro Gacci, Christian Gratzke, et al. Summary Paper on the 2023 European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms. Eur Urol. 2023;84:207–22
Authors: Francesco Montorsi, Paolo Capogrosso, Federico Dehò, Andrea Salonia
Journal: European Urology (2023)
Germline pathogenic variants in neuroblastoma patients are enriched in <i>BARD1</i> and predict worse survival
Authors: Jung Kim, Zalman Vaksman, Laura E Egolf, Rebecca Kaufman, J Perry Evans, Karina L Conkrite, Arnavaz Danesh, Gonzalo Lopez, Michael P Randall, Maiah H Dent, Lance M Farra, Neil L Menghani, Malwina Dymek, Heena Desai, Ryan Hausler, Belynda Hicks, Jaime M Guidry Auvil, Daniela S Gerhard, Hakon Hakonarson, Kara N Maxwell, Kristina A Cole, Trevor J Pugh, Kristopher R Bosse, Javed Khan, Jun S Wei, John M Maris, Douglas R Stewart, Sharon J Diskin
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Neuroblastoma is an embryonal cancer of the developing sympathetic nervous system. The genetic contribution of rare pathogenic or likely pathogenic germline variants in patients without a family history remains unclear. Methods Germline DNA sequencing was performed on 786 neuroblastoma patients. The frequency of rare cancer predisposition gene pathogenic or likely pathogenic variants in patients was compared with 2 cancer-free control cohorts. Matched tumor DNA sequencing was evaluated for second hits, and germline DNA array data from 5585 neuroblastoma patients and 23 505 cancer-free control children were analyzed to identify rare germline copy number variants. Patients with germline pathogenic or likely pathogenic variants were compared with those without to test for association with clinical characteristics, tumor features, and survival. Results We observed 116 pathogenic or likely pathogenic variants involving 13.9% (109 of 786) of neuroblastoma patients, representing a statistically significant excess burden compared with cancer-free participants (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.27 to 2.00). BARD1 harbored the most statistically significant enrichment of pathogenic or likely pathogenic variants (OR = 32.30, 95% CI = 6.44 to 310.35). Rare germline copy number variants disrupting BARD1 were identified in patients but absent in cancer-free participants (OR = 29.47, 95% CI = 1.52 to 570.70). Patients harboring a germline pathogenic or likely pathogenic variant had a worse overall survival compared with those without (P = 8.6 x 10−3). Conclusions BARD1 is an important neuroblastoma predisposition gene harboring both common and rare germline pathogenic or likely pathogenic variations. The presence of any germline pathogenic or likely pathogenic variant in a cancer predisposition gene was independently predictive of worse overall survival. As centers move toward paired tumor-normal sequencing at diagnosis, efforts should be made to centralize data and provide an infrastructure to support cooperative longitudinal prospective studies of germline pathogenic variation.
Prospective analysis to determine barriers to <scp>allogeneic hematopoietic cell transplantation</scp> in patients with acute leukemia
Authors: Karthik Nath, Jasme Lee, Theresa A. Elko, Lauren Levy, Elaina Preston, Sean M. Devlin, Doris M. Ponce, Richard J. Lin, Brian C. Shaffer, Christina Cho, Ioannis Politikos, Ann A. Jakubowski, Jae H. Park, Raajit Rampal, Miguel‐Angel Perales, Martin S. Tallman, Juliet N. Barker, Ellin Berman, Roni Tamari, Eytan Stein, Sergio A. Giralt, Boglarka Gyurkocza
Journal: American Journal of Hematology (2023)

Abstract Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative treatment for patients with acute leukemia. Despite this, studies have shown that only a minority of patients ultimately proceed to allo‐HCT. The primary objective of this prospective, observational study was to identify the rate of allo‐HCT in patients for whom it was recommended, and reasons why patients deemed appropriate and eligible for HCT did not subsequently undergo transplant. Between April 2016 and April 2021, adult patients with newly diagnosed or relapsed/refractory acute leukemia were enrolled at the time of induction/reinduction therapy. Initial transplantation workup and allo‐HCT recommendations were made during the early phase of induction/reinduction. Of the 307 enrolled patients, allo‐HCT was recommended to 85% ( n = 259), of whom 66% ( n = 170) underwent transplant. Donor sources comprised 54% human leukocyte antigen (HLA)‐matched unrelated donors, 20% HLA‐matched sibling donors and HLA‐mismatched graft sources with 15% umbilical cord blood units, 8% HLA‐mismatched unrelated donors, and 4% HLA‐haploidentical donors. The most common reason for transplant disqualification in the 89 patients in whom it was initially recommended was persistent/relapsed disease (70%), followed by early patient death (10%). In this prospective study, we report a high allo‐HCT rate, which may be due to early transplant referral and workup. The main allo‐HCT barrier was disease control, followed by early patient death. With the increasing availability of HLA‐mismatched graft sources, the lack of donor availability was not a transplant barrier. Further development of novel transplant strategies for patients not achieving remission and improvements in induction regimens could result in increased allo‐HCT utilization.
Threatening the Global AIDS Response — Obstacles to PEPFAR’s Reauthorization
Authors: Salim S. Abdool Karim, Francoise Barre-Sinoussi, Harold E. Varmus, David Serwadda, Elizabeth Bukusi, Souleymane M’boup, Adeeba Kamarulzaman, Soumya Swaminathan, Jean W. Pape
Journal: New England Journal of Medicine (2023)
Asparagine endopeptidase protects podocytes in adriamycin-induced nephropathy by regulating actin dynamics through cleaving transgelin
Authors: Yang Qiu, Chuntao Lei, Jieyu Zeng, Yaru Xie, Yiling Cao, Qian Yuan, Hua Su, Zhentao Zhang, Chun Zhang
Journal: Molecular Therapy (2023)

Focal segmental glomerulosclerosis (FSGS) is the most common glomerular disorder causing end-stage renal diseases worldwide. Central to the pathogenesis of FSGS is podocyte dysfunction, which is induced by diverse insults. However, the mechanism governing podocyte injury and repair remains largely unexplored. Asparagine endopeptidase (AEP), a lysosomal protease, regulates substrates by residue-specific cleavage or degradation. We identified the increased AEP expression in the primary proteinuria model which was induced by adriamycin (ADR) to mimic human FSGS. In vivo, global AEP knockout mice manifested increased injury-susceptibility of podocytes in ADR-induced nephropathy (ADRN). Podocyte-specific AEP knockout mice exhibited much more severe glomerular lesions and podocyte injury after ADR injection. In contrast, podocyte-specific augmentation of AEP in mice protected against ADRN. In vitro, knockdown and overexpression of AEP in human podocytes revealed the cytoprotection of AEP as a cytoskeleton regulator. Furthermore, transgelin, an actin-binding protein regulating actin dynamics, was cleaved by AEP, and, as a result, removed its actin-binding regulatory domain. The truncated transgelin regulated podocyte actin dynamics and repressed podocyte hypermotility, compared to the native full-length transgelin. Together, our data reveal a link between lysosomal protease AEP and podocyte cytoskeletal homeostasis, which suggests a potential therapeutic role for AEP in proteinuria disease.
CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer
Authors: Changsong Qi, Tong Xie, Jun Zhou, Xicheng Wang, Jifang Gong, Xiaotian Zhang, Jian Li, Jiajia Yuan, Chang Liu, Lin Shen
Journal: Journal of Hematology & Oncology (2023)

Abstract Pancreatic cancer lacks effective therapy. Here, we reported two metastatic pancreatic cancer patients administrated with Claudin 18.2 (CLDN 18.2) CART therapy after the failure of standard therapy (NCT04581473 and NCT03874897). In case 1, with CLDN 18.2 expression of 2+, 70%, 250 × 10 6 cells were infused after lymphodepletion. Grade 1 cytokine release syndrome (CRS) occurred on d1 which was later controlled by tocilizumab. Partial response (PR) was achieved according to RECIST v1.1, with great shrinkage of lung metastasis. An increasing CD8+ T cell and Treg cells and declining CD4+ T cell and B cell were observed. In case 2, IHC result of ClDN18.2 showed 3+, 60%. 250 × 10 6 CLDN18.2 CART cells were subsequently administered. Patient experienced grade 2 CRS, which was controlled with tocilizumab. Target lesions of lung metastasis further achieved complete response. Similar increasing CD8+ T cell and Treg cell was detected from peripheral blood. Elevating IL-8 and declining TGF-β1 were also observed. The tumor is still under well control until the last follow-up on July 18, 2023.
Target protein degradation by protacs: A budding cancer treatment strategy
Authors: Diksha Choudhary, Amritpal Kaur, Pargat Singh, Gaurav Chaudhary, Rajwinder Kaur, Mohammad F. Bayan, Balakumar Chandrasekaran, Saeed M. Marji, Reema Ayman
Journal: Pharmacology & Therapeutics (2023)
The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: A Re-Assessment of the International Thymic Malignancy Interest Group/International Association for the Study of Lung Cancer Lymph Node Map for Thymic Epithelial Tumors for the Forthcoming Ninth Edition of the TNM Classification of Malignant Tumors
Authors: Edith M. Marom, Wentao Fang, Enrico Ruffini, Frank Detterbeck, Usman Ahmad, Sarit Appel, Andrea Bille, Souheil Boubia, Cecilia Brambilla, Vanessa Cilento, Ayten Kayi Cangir, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Nicolas Girard, Emily Goren, Francesco Guerrera, James Huang, Maurizio Infante, Dong-Kwan Kim, Marco Lucchi, Mirella Marino, Andrew G. Nicholson, Meinoshin Okumura, Ramon Rami-Porta, Andreas Rimner, Charles B. Simone, Hisao Asamura
Journal: Journal of Thoracic Oncology (2023)

A lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the eighth edition of the TNM classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but it was largely empirical because of limited available data. Dissemination of the map and implementation of a standard thymic stage classification across the world in 2017 have provided more consistent and granular data.More than twice as many cases of node involvement are available for analysis in the current database compared with that of the eighth edition database, allowing validation of many aspects of the eighth edition map. This article details the process and considerations for refinement of the thymic map for the ninth TNM used by the Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer. The committee evaluated a large international collaborative data set, published anatomical and clinical studies pertaining to lymph node spread from thymic epithelial tumors, in conjunction with the analysis underlying refinements of the TNM components for the ninth edition TNM classification.The node map boundaries of the N1 and N2 categories remain unchanged. Visual clarifications have been added to the nomenclature of nodal stations within these regions.On the basis of the recommendation to keep the N component unchanged for the ninth edition TNM classification, the lymph node map remains unchanged as well; however, clarifications have been added to facilitate clinical use.
The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors
Authors: Enrico Ruffini, James Huang, Vanessa Cilento, Emily Goren, Frank Detterbeck, Usman Ahmad, Sarit Appel, Andrea Bille, Souheil Boubia, Cecilia Brambilla, Ayten Kayi Cangir, Conrad Falkson, Wentao Fang, Pier Luigi Filosso, Giuseppe Giaccone, Nicolas Girard, Francesco Guerrera, Maurizio Infante, Dong Kwan Kim, Marco Lucchi, Mirella Marino, Edith M Marom, Andrew G Nicholson, Meinoshin Okumura, Ramon Rami-Porta, Andreas Rimner, Charles B Simone, Hisao Asamura
Journal: Journal of Thoracic Oncology (2023)
Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling
Authors: Yong Rao, Rui Su, Chenyan Wu, Xingxing Chai, Jinjian Li, Guanyu Yang, Junjie Wu, Tingting Fu, Zhongping Jiang, Zhikai Guo, Congjun Xu, Ling Huang
Journal: Acta Pharmaceutica Sinica B (2023)

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus
Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection
Authors: Xintong Zhao, Jing Feng, Jie Zhang, Zunsheng Han, Yuhua Hu, Hui-Hui Shao, Tianlei Li, Jie Xia, Kangfan Lei, Weiping Wang, Fangfang Lai, Yuan Lin, Bo Liu, Kun Zhang, Chi Zhang, Qingyun Yang, Xinyu Luo, Hanyilan Zhang, Chuang Li, Wenxuan Zhang, Song Wu
Journal: Acta Pharmaceutica Sinica B (2023)

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.
circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-β signalling pathway-mediated activation of MMPs in pancreatic cancer
Authors: Zhongjie Zhao, Wenbo Yang, Rui Kong, Yangyang Zhang, Le Li, Zengfu Song, Hongze Chen, Yan Luo, Tao Zhang, Chundong Cheng, Guanqun Li, Danxi Liu, Xinglong Geng, Hua Chen, Yongwei Wang, Shangha Pan, Jisheng Hu, Bei Sun
Journal: Molecular Cancer (2023)

Abstract Background Among digestive tract tumours, pancreatic ductal adenocarcinoma (PDAC) shows the highest mortality trend. Moreover, although PDAC metastasis remains a leading cause of cancer-related deaths, the biological mechanism is poorly understood. Recent evidence demonstrates that circular RNAs (circRNAs) play important roles in PDAC progression. Methods Differentially expressed circRNAs in normal and PDAC tissues were screened via bioinformatics analysis. Sanger sequencing, RNase R and actinomycin D assays were performed to confirm the loop structure of circEIF3I. In vitro and in vivo functional experiments were conducted to assess the role of circEIF3I in PDAC. MS2-tagged RNA affinity purification, mass spectrometry, RNA immunoprecipitation, RNA pull-down assay, fluorescence in situ hybridization, immunofluorescence and RNA–protein interaction simulation and analysis were performed to identify circEIF3I-interacting proteins. The effects of circEIF3I on the interactions of SMAD3 with TGFβRI or AP2A1 were measured through co-immunoprecipitation and western blotting. Results A microarray data analysis showed that circEIF3I was highly expressed in PDAC cells and correlated with TNM stage and poor prognosis. Functional experiments in vitro and in vivo revealed that circEIF3I accelerated PDAC cells migration, invasion and metastasis by increasing MMPs expression and activity. Mechanistic research indicated that circEIF3I binds to the MH2 domain of SMAD3 and increases SMAD3 phosphorylation by strengthening the interactions between SMAD3 and TGFβRI on early endosomes. Moreover, AP2A1 binds with circEIF3I directly and promotes circEIF3I-bound SMAD3 recruitment to TGFβRI on early endosomes. Finally, we found that circEif3i exerts biological functions in mice similar to those of circEIF3I in humans PDAC. Conclusions Our study reveals that circEIF3I promotes pancreatic cancer progression. circEIF3I is a molecular scaffold that interacts with SMAD3 and AP2A1 to form a ternary complex, that facilitates the recruitment of SMAD3 to early endosomes and then activates the TGF-β signalling pathway. Hence, circEIF3I is a potential prognostic biomarker and therapeutic target in PDAC.
Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health
Authors: Shirley Cohen-Mekelburg, Ariel Jordan, Brooke Kenney, Helen J. Burgess, Joy W. Chang, Hsou Mei Hu, Elliot Tapper, Kenneth M. Langa, Deborah A. Levine, Akbar K. Waljee
Journal: Clinical Gastroenterology and Hepatology (2023)